BACKGROUND: The authors examined the role of dopamine and serotonin transporter genetic polymorphisms in clinical and cognitive features of subjects with late-life depression, and in preferential treatment response to the combination of methylphenidate and citalopram. METHOD: The authors studied fifteen outpatients with major depression in a pilot ten-week double-blind trial ofmethylphenidate combined with citalopram and compared to citalopram and placebo. Response was defined as a score on the Hamilton Depression Rating Scale (24-item) of less than 10. All underwent genotyping to determine the dopamine (DAT VNTR) and serotonin (5HTTLPR) transporter polymorphisms. RESULTS: Subjects with DAT VNTR 10/10 genotype had greater cognitive executive dysfunction at baseline compared to others. However, they responded preferentially to methylphenidate added to citalopram with a greater reduction in depression severity over time compared to other subjects. CONCLUSIONS:DAT VNTR 10/10 genotype may be associated with an endophenotype of late-life depression with executive dysfunction that responds preferentially to methylphenidate added to a selective serotonin reuptake inhibitor, which warrants replication in a large sample.
RCT Entities:
BACKGROUND: The authors examined the role of dopamine and serotonin transporter genetic polymorphisms in clinical and cognitive features of subjects with late-life depression, and in preferential treatment response to the combination of methylphenidate and citalopram. METHOD: The authors studied fifteen outpatients with major depression in a pilot ten-week double-blind trial of methylphenidate combined with citalopram and compared to citalopram and placebo. Response was defined as a score on the Hamilton Depression Rating Scale (24-item) of less than 10. All underwent genotyping to determine the dopamine (DAT VNTR) and serotonin (5HTTLPR) transporter polymorphisms. RESULTS: Subjects with DAT VNTR 10/10 genotype had greater cognitive executive dysfunction at baseline compared to others. However, they responded preferentially to methylphenidate added to citalopram with a greater reduction in depression severity over time compared to other subjects. CONCLUSIONS: DAT VNTR 10/10 genotype may be associated with an endophenotype of late-life depression with executive dysfunction that responds preferentially to methylphenidate added to a selective serotonin reuptake inhibitor, which warrants replication in a large sample.
Authors: Harris A Eyre; Ascia Eskin; Stanley F Nelson; Natalie M St Cyr; Prabha Siddarth; Bernhard T Baune; Helen Lavretsky Journal: Int J Geriatr Psychiatry Date: 2015-10-15 Impact factor: 3.485